Program Director/Principal Investigator (Last, First, Middle): O r c h a r d , T r e v o r J . PROJECT SUMMARY (See instruclions): Unlike type 2 diabetes, where prevention is possible, type 1 diabetes is currently neither preventable nor curable and its Incidence continues to rise approximately 3% peryr. Thus, the continuing investigation of type 1 diabetes complications remains imperative. The Epidemiology of Diabetes Complications (EDC) study has examined the prevalence and incidence of and risk factors contributing to the diabetes complications for 25 yrs. The study population is a well defined cohort of childhood onset type 1 diabetes identified from the Children's Hospital of Pittsburgh Registry (diagnosis: 1950-80). All 658 participants attending a clinical exam at study entry (1986-88) have been subsequently followed for up to 25 yrs, leading to over 150 peer reviewed publications. A number of striking observations were made during the last phase of the study which have given rise to questions and hypotheses this continuation will continue to address. These include the increasingly complex interaction between various pro- and anti-glycoxidative and inflammatory cytokines, as well as the rapidly changing natural history of complications which provides further insight into the interrelationships of, and specific risk factors for, complications, and renders historic data outdated for health care and insurance purposes. The current proposal, therefore, focuses on further assessment of complication development for a total follow up period of 30 yrs, thus allowing reasonably stable estimates of complication development over 40 yrs duration of childhood onset type 1 diabetes. This gives the opportunity to document morbidity risk and to estimate life expectancy in the modern era, i.e. for those diagnosed in 1965-80 and who have had more than half their diabetes duration since the availability of HbA1c testing and self monitoring of blood glucose. The roles of glycemic, oxidative and inflammatory stress, and the host's responses they invoke, on complication development will be another major focus along with women's health issues and continuing a number of collaborations. Finally, we will evaluate skin advanced glycosylation end products as a complication predictor for 232 individuals with at least one such assessment. This will be facilitated by continuing the annual surveys and, at 30 yrs of follow up, a full exam. RELEVANCE (See instructions): Type 1 diabetes is currently neither preventable nor curable and its incidence continues to rise about 3% per yr. Thus, the continuing investigation of type 1 diabetes complications remains imperative. The current proposal will not only provide insight on complication incidence, but also fill gaps in knowledge on T1D women's health issues, and the role of stress and host's response and skin AGE on complications.